IFN alpha 2b induces apoptosis and proteasome-mediated degradation of p27(Kip1) in a human lung cancer cell line

IFNs are a family of cytokines involved in antiviral defense, cell growth r egulation and immune activation. IFNs either inhibit cell proliferation or control apoptosis depending on factors such as cell type and state of cell differentiation. It is important to determine how IFN-induced gene products interact with other cellular proteins to produce these responses. We have investigated the effect of IFN alpha 2b on a human small cell lung carcinom a (SCLC) cell line H82. We have found that IFN alpha efficiently induces ap optosis in H82 cells. The induction of apoptosis by IFN alpha 2b is accompa nied by decreased levels of c-myc and Cdk2. We have also observed that in H 82 cells IFN alpha induces downregulation of p27 and this is in contrast to the upregulation of p27 observed in other cell types where IFNs induce cel l cycle arrest. IFN alpha -induced downregulation of p27 is due to protein destabilization and can be prevented by the proteasome inhibitor LLnL. The data suggest that in H82 cells, IFN alpha 2b induces degradation of p27(Kip 1) independently of CDK2 kinase activity and through a ubiquitin or ubiquit in-related pathway and that the degradation of p27(Kip1) could be a molecul ar event of importance for IFN-induced apoptosis in cancer cells.